TY  - JOUR
AB  - Nonalcoholic fatty liver disease (NAFLD) is a very common hepatic pathology featuring steatosis and is linked to obesity and related conditions, such as the metabolic syndrome. When hepatic steatosis is accompanied by inflammation, the disorder is defined as nonalcoholic steatohepatitis (NASH), which in turn can progress toward fibrosis development that can ultimately result in cirrhosis. Cells of innate immunity, such as neutrophils or macrophages, are central regulators of NASH-related inflammation. Recent studies utilizing new experimental technologies, such as single-cell RNA sequencing, have revealed substantial heterogeneity within the macrophage populations of the liver, suggesting distinct functions of liver-resident Kupffer cells and recruited monocyte-derived macrophages with regards to regulation of liver inflammation and progression of NASH pathogenesis. Herein, we discuss recent developments concerning the function of innate immune cell subsets in NAFLD and NASH.
AU  - Nati, M.
AU  - Chung, K.J.*
AU  - Chavakis, T.
C1  - 62917
C2  - 50993
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 1-11
TI  - The role of innate immune cells in nonalcoholic fatty liver disease.
JO  - J. Innate Immun.
PB  - Karger
PY  - 2021
SN  - 1662-811X
ER  - 

TY  - JOUR
AB  - Different liver cell types are endowed with immunological properties, including cell-intrinsic innate immune functions that are important to initially control pathogen infections. However, a full landscape of expression and functionality of the innate immune signaling pathways in the major human liver cells is still missing. In order to comparatively characterize these pathways, we purified primary human hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells (LSEC), and Kupffer cells (KC) from human liver resections. We assessed mRNA and protein expression level of the major innate immune sensors, as well as checkpoint-inhibitor ligands in the purified cells, and found Toll-like receptors (TLR), RIG-I-like receptors, as well as several DNA cytosolic sensors to be expressed in the liver microenvironment. Amongst the cells tested, KC were shown to be most broadly active upon stimulation with PRR ligands emphasizing their predominant role in innate immune sensing the liver microenvironment. By KC immortalization, we generated a cell line that retained higher innate immune functionality as compared to THP1 cells, which are routinely used to study monocyte/macrophages functions. Our findings and the establishment of the KC line will help to understand immune mechanisms behind antiviral effects of TLR agonists or checkpoint inhibitors, which are in current preclinical or clinical development.
AU  - Faure-Dupuy, S.*
AU  - Vegna, S.*
AU  - Aillot, L.*
AU  - Dimier, L.*
AU  - Esser, K.
AU  - Broxtermann, M.
AU  - Bonnin, M.*
AU  - Bendriss-Vermare, N.*
AU  - Rivoire, M.*
AU  - Passot, G.*
AU  - Lesurtel, M.*
AU  - Mabrut, J.Y.*
AU  - Ducerf, C.*
AU  - Salvetti, A.*
AU  - Protzer, U.
AU  - Zoulim, F.*
AU  - Durantel, D.*
AU  - Lucifora, J.*
C1  - 53873
C2  - 45056
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 339–348 
TI  - Characterization of pattern recognition receptor expression and functionality in liver primary cells and derived cell lines.
JO  - J. Innate Immun.
VL  - 10
IS  - 4
PB  - Karger
PY  - 2018
SN  - 1662-811X
ER  - 

TY  - JOUR
AB  - The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract. (c) 2018 S. Karger AG, Basel
AU  - Hartl, D.*
AU  - Tirouvanziam, R.*
AU  - Laval, J.*
AU  - Greene, C.M.*
AU  - Habiel, D.M.*
AU  - Sharma, L.*
AU  - Yildirim, A.Ö.
AU  - Dela Cruz, C.S.*
AU  - Hogaboam, C.M.*
C1  - 52960
C2  - 44670
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 487-501
TI  - Innate immunity of the lung: From basic mechanisms to translational medicine.
JO  - J. Innate Immun.
VL  - 10
IS  - 5-6
PB  - Karger
PY  - 2018
SN  - 1662-811X
ER  - 

TY  - JOUR
AB  - The CD6 scavenger receptor is known to be expressed on virtually all T cells and is supposed to be involved in costimulation, synapse formation, thymic selection and leukocyte migration. Here, we demonstrate that CD6 is differentially expressed by a subpopulation of peripheral CD56(dim) natu- ral killer (NK) cells and absent on CD56(bright) NK cells. CD56(dim)CD16(+) cells represent the major NK subset in the periphery, and most cells within this group are positive for CD6. Most killer immunoglobulin-like receptor- and immunoglobulin-like transcript-positive cells also belong to the CD6(+) subpopulation, as expected from their restricted expression on CD56(dim) NK cells. In addition, CD6(+) NK cells are similar to the newly identified CD94(low)CD56(dim) NK subpopulation and most distant from the recently defined CD27(+) NK subpopulation based on the reverse correlation of expression between CD6 and CD27, a marker associated primarily with CD56(bright) NK cells. With respect to CD6 function on NK cells, direct CD6 triggering did not result in degranulation but induced secretion of cytokines (interferon-γ and tumor necrosis factor-α) and chemokines [CXCL10 (IP-10), CXCL1 (GRO-α)]. Thus, CD6 expression on peripheral NK cells marks a novel CD56(dim) subpopulation associated with distinct patterns of cytokine and chemokine secretion.
AU  - Braun, M.*
AU  - Müller, B.*
AU  - ter Meer, D.*
AU  - Raffegerst, S.H.
AU  - Simm, B.*
AU  - Wilde, S.*
AU  - Spranger, S.*
AU  - Ellwart, J.*
AU  - Mosetter, B.*
AU  - Umansky, L.*
AU  - Lerchl, T.*
AU  - Schendel, D.J.
AU  - Falk, C.S.*
C1  - 6039
C2  - 28611
SP  - 420-434
TI  - The CD6 scavenger receptor is differentially expressed on a CD56 natural killer cell subpopulation and contributes to natural killer-derived cytokine and chemokine secretion.
JO  - J. Innate Immun.
VL  - 3
IS  - 4
PB  - Karger
PY  - 2011
SN  - 1662-811X
ER  -